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Peanut Allergy 2009

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Peanut Allergy 2009

  1. 1. Narissara Suratannon,MD. What's New in Peanut Allergy?
  2. 2. Outline <ul><li>Epidermiology in western and eastern countries </li></ul><ul><li>Cross reactivity of peanut among other legumes and tree nut </li></ul><ul><li>How roasting peanuts increase their allergenicity </li></ul><ul><li>Diagnosis of peanut allergy </li></ul><ul><li>Natural history of peanut allergy </li></ul><ul><li>Factors associated developing of peanut allergy </li></ul><ul><li>New treatment of peanut allergy </li></ul>
  3. 3. Introduction <ul><li>Food allergy is the leading cause of anaphylaxis in Western Europe an d USA </li></ul><ul><li>In USA , food allergy accounts for : </li></ul><ul><ul><li>- 30 , 000 anaphylactic reactions </li></ul></ul><ul><ul><li>- 2000 hospital admissions </li></ul></ul><ul><ul><li>- 200 death s </li></ul></ul><ul><li>Peanut s and treenuts are the vast majority of life-threatening or fatal reactions to food </li></ul>A. Wesley Burks . Lancet 2008; 371: 1538–46
  4. 4. Epidermiology <ul><li>2-4 fold increasing </li></ul><ul><li>P revalence of sensitisation </li></ul><ul><li>- I n UK rose from 1. 3 % to 3 . 2% [ 1989 and 1995 ] </li></ul><ul><li> (Grundy.JACI 2002) </li></ul><ul><li>- In US 8.6% [ 1988 – 1994] (Arbes JACI 2005) </li></ul><ul><li>Prevalence of clinical reactions </li></ul><ul><li>- 0.5 to 1.0% in UK (Grundy.JACI 2002) </li></ul><ul><li>- 0.4 to 0.8% in US [1997-2002] (Sicherer.JACI 2003) </li></ul><ul><li>- 1.34% in Canada (Kagan JACI 2003) </li></ul><ul><li>- 1.9% in Australia () </li></ul>A. Wesley Burks . JACI 200 9 ; 123 (2) : 424 – 5
  5. 5. Parent-reported adverse food reactions in Hong Kong Chinese pre-schoolers:epidemiology, clinical spectrum and risk factors Leung et al.Ped AI 2009: 20: 339–346.
  6. 6. Chieng et al. Clinical and Experimental Allergy 2007: 37 : 1055–61
  7. 7. Legumes Bean Pea Lentil Peanut Lupine
  8. 8. Legumes <ul><li>ประกอบด้วย </li></ul><ul><li>Bean : ถั่วที่ออกเป็นฝัก เมล็ดไม่กลม </li></ul><ul><li>Pea : ถั่วเมล็ดกลม (Green Pea) – ถั่วลันเตา chickpea </li></ul><ul><li>Lentil แบนเหมือนตาคน </li></ul><ul><li>Peanuts </li></ul><ul><li>Multiple sensitization appeared to be the rule in the legume family </li></ul><ul><li>Cross-reaction are uncommon </li></ul><ul><li>P.1146 </li></ul>
  9. 9. Legumes <ul><li>Multiple sensitization appeared to be the rule </li></ul><ul><li>Barnett et al screened sera from 40 patients with </li></ul><ul><li>peanut allergy against 10 other legumes and </li></ul><ul><li>demonstrated IgE binding to multiple legumes for </li></ul><ul><li>38% of patients ( JACI1987;79:433-8) </li></ul><ul><li>However, clinical cross-reactions are uncommon </li></ul>Scott H. Sicherer, JACI 2001;108:881-90
  10. 10. Cros-allergenicity in the legume botanical family in children with food hypersensitivity Jan Bernhisel-Broadbent, MD, and Huge A. Sampson, MD JACI 1989;83:435-40 <ul><li>82/186 (44%): </li></ul><ul><li>>= 1 positive SPT </li></ul><ul><li>Clinical cross- </li></ul><ul><li>reaction:unlikely </li></ul><ul><li>to occur </li></ul><ul><li>mild reactions </li></ul>
  11. 11. Clinical Cross-Reactions in Legume Family <ul><li>Regional dietary habits may influence </li></ul><ul><li>the epidemiology of legume allergy </li></ul><ul><li>M ultiple legume allergy may occur on </li></ul><ul><li>those who reacting to lupine ,lentil, </li></ul><ul><li>chickpea </li></ul><ul><li>In France, 11 (44%) of 24 had positive </li></ul><ul><li>skin test to lupine, and 7 of 8 subjects </li></ul><ul><li>had positive oral challenge tests </li></ul><ul><li>(Vautrin et al.JACI 1999;104:883-8) </li></ul>Scott H. Sicherer, JACI 2001;108:881-90
  12. 12. Clinical Cross-Reactions in Legume Family <ul><li>However, in Italy; lupine-enriched pasta can be tolerated by most subjects suffering from peanut allergy, only 2/12 children had positive reactions </li></ul><ul><li>( Fiocchi et al.Clin Exp Aller 2009;article in press) </li></ul><ul><li>In Spain, 6/ 22 children with lentil allergy had reactions to chickpea, 2 / 22 to other pea s , and 1/22 to green bean </li></ul><ul><li>( Pascual et al.JACI 1999 ;103:154- 8 ) </li></ul>
  13. 13. Co-allergy between peanut and tree nut <ul><li>Isolate d peanut allergy 3482 registrants(68%) </li></ul><ul><li>I solated tree nut allergy by 464 (9%) </li></ul><ul><li>A llergy to both foods by 1203 (23%) </li></ul>JACI 2001;108:128-32
  14. 14. JACI 2001;107:367-74
  15. 15. P rophylactically avoid tree nut s Should we recommend? <ul><li>Varying results causing by different populations, types of diagnosis </li></ul><ul><li>No studies that document the reaction rate using blinded oral food challenges </li></ul><ul><li>Complete avoidance of tree nuts was recommend except one that were previously tolerated </li></ul>Sicherer et al.JACI 2001;108:128-32
  16. 16. Reasons for Recommendation <ul><li>Concerning that TN sensitivity appears to be severe and long-lived </li></ul><ul><li>The potential for cross contamination </li></ul><ul><li>It is often difficult to identify specific nuts in various processed foods </li></ul>Sicherer et al.JACI 2001;108:128-32
  17. 17. Peanut Allergens <ul><li>F ood allergens are </li></ul><ul><ul><li>- glycoproteins, 10-70 kd </li></ul></ul><ul><ul><li>water-soluble </li></ul></ul><ul><ul><li>resistant to heat, acid, and proteolysis which enables them to sensitize GI tract </li></ul></ul>Laurie A. Lee, A. Wesley Burks . Frontiers in Bioscience 2009; 14, 3361-71 , Table from Middleton 7’th edition
  18. 18. Maillard reaction JACI 2000;106:763-8 (MRPs)
  19. 19. JACI 2000;106:763-8 JACI 2001;107:1077-81
  20. 20. Diagnosis of Peanut Allergy
  21. 21. Clin Exp Aller.2000: 30 ; 1540 - 46
  22. 22. Clin Exp Aller.2000: 30 ; 1540 - 46
  23. 23. Roberts et al.JACI 2005;115:1291-6 Wheal size >= 8 mm or >= 15 kUA/L of specific IgE was correlate with positive oral challenge test of peanut allergy Outcome No compare group Compare What size of skin prick test and which levels of specific IgE that will be correlate with oral challenge test Intervention Pt. under 16 yr. who was suspected FA (n=121) and from ALSPAC study who SPT +ve (n=40) Patient
  24. 24. PPV = 94.4%, S pecificity = 98.5% , NPV = 57.3% , sensitivity = 25.4%. Roberts et al.JACI 2005;115:1291-6
  25. 25. <ul><li>PPV of a specific IgE of 15-kUA/L = 91.3% </li></ul><ul><li>Specificity = 96.8% , NPV = 53.0% , Sensitivity = 28.4% </li></ul>Roberts et al.JACI 2005;115:1291-6
  26. 26. <ul><li>Although the likelihood of clinical reactivity increases with the size of </li></ul><ul><li>the skin test reaction and level of food-specific IgE </li></ul><ul><li>they have no correlation with the severity of the reaction </li></ul><ul><li>IgE binding to many </li></ul><ul><li>epitopes correlated with a history of multisystem reactions </li></ul><ul><li>to peanut whereas IgE binding to only a few epitopes </li></ul><ul><li>correlated with reactions limited to the skin. </li></ul>Laurie A. Lee, A. Wesley Burks . Frontiers in Bioscience 2009; 14, 3361-71
  27. 27. Predictors for severe diseases <ul><li>Broad epitope diversity (Median =9.5) tend to more severe allergic reactions than who have few epitopes binding (Median =2) </li></ul>Shreffler et al.JACI 2004;113:776-82
  28. 28. Natural History of Peanut Allergy
  29. 29. Natural History <ul><li>Mostly IgE-mediated reactions </li></ul><ul><li>The mean age of diagnosis : 14-18 months </li></ul><ul><li>Symptoms occur following the first known peanut ingestion in 75% of those children </li></ul><ul><li>Almost always permanent </li></ul><ul><ul><li>Incidence in children = adults at the similar rate (Sicherer JACI 1999 from US digital phone survey) </li></ul></ul><ul><ul><li>After 10 years pass, study groups still could not tolerate peanut (Bock and Atkins JACI 1989) </li></ul></ul><ul><li>However, a subset of young peanut-allergic children (20%) indeed outgrows allergy </li></ul>Laurie A. Lee, A. Wesley Burks . Frontiers in Bioscience 2009; 14, 3361-71 David Fleischer.Current Allergy and Asth Reports 2007:7 ; 1 75 - 8 1
  30. 30. JACI 2008;121:731-6 Skin prick test >= 6 mm and specific IgE to peanut >= 3 kUA/L before 2 years of age are predictors of persistent peanut allergy Outcome Remitters (n=49) Compare Find out what are predictors of remission (clinical, lab tests) Intervention Children under 2 years who had peanut allergy ; non-remitters (n= 218) Patient
  31. 31. JACI 2008;121:731-6
  32. 32. Recurrent Peanut Allergy <ul><li>Estimated recurrent rates 7.9% </li></ul><ul><li>Risk : Consumed peanut infrequently </li></ul><ul><li>Recommendation : Foods should be consumed regularly and continue to carry a SIE until demenstrated persist tolerance for 1 or 2 yr. </li></ul><ul><li>However, it is hard.. </li></ul><ul><ul><li>Nearly half of outgrown patients : limited intake to products that “may contain peanut” </li></ul></ul><ul><ul><li>To incorporate peanut into their diet after years of strict avoidance : a way of life that difficult to change </li></ul></ul>David Fleischer.Current Allergy and Asth Reports 2007:7 ; 1 75 - 8 1
  33. 33. Factors associated Developing of Peanut Allergy
  34. 34. <ul><li>Prevalence of peanut allergy was rising despite many strategies </li></ul><ul><li>72 to 81% of presentation of peanut occur on first exposure to peanut </li></ul>Questions? Others factors contributing for peanut allergy?? Failure to follow guideline?? Delayed exposure strategies are failure?? Other routes causing sensitization??
  35. 35. NEJM 2003:348;977-85 Maternal peanut consumption , positive cord-blood specific IgE to peanut :not increased risk of PA but .. Outcome Eczematous children without peanut allergy (n=70) , healthy controls (n=140) Compare Find factors associated with the development of peanut allergy Intervention Children with had peanut allergy aged under 38 months (n=49,36) from ALPSAC study Patient (questionaire, OC)
  36. 36. NEJM 2003:348;977-85
  37. 37. Failure to follow guideline?? <ul><li>In 2000, AAP, based on expert opinion, suggested nursing mothers of at-risk infants to eliminate peanuts from their diet and introduction of peanut should be delayed until 3 years of age </li></ul><ul><li>In a survey of 957 mothers in UK (Hourihane et al. JACI 2007) </li></ul><ul><ul><li>61% recalled hearing the advice about peanuts </li></ul></ul><ul><ul><li>3.8 % stopped consuming peanuts while pregnant </li></ul></ul>A. Wesley Burks . Lancet 2008; 371: 1538–46
  38. 38. FAQ : prevalence of peanut allergy 10,786 children aged 4-19 years in 24 schools (13 in UK, 11 in Israel) 8,600 children 1960 not-returned 226 was excluded Israel = 4657 UK = 3943 FFQ : mothers & infants consumption questionnaire Mothers of Jewish infants aged 8-14 months (n=176) Israel = 99 UK = 77 Du Toit et al.JACI 2008;122:984-91 81.8%
  39. 39. JACI 2008;122:984-91 <ul><li>47/81 children with questionaire-based diagnosis of PA underwent </li></ul><ul><li>clinical assessment; 36/47 (77%) had PA , the rest are peanut tolerant </li></ul>
  40. 40. JACI 2008;122:984-91
  41. 41. JACI 2008;122:984-91
  42. 42. The largest and most significant difference between UK and Isarel was in age of introduction of peanut (P<0.001) Du loit et al.JACI 2008;122:984-91
  43. 43. Could different methods of preparing peanut be responsible for different rates? Du loit et al.JACI 2008;122:984-91 Summery : there was a strong inverse association between peanut consumption in infancy and prevalence of PA in childhood
  44. 44. Fox et al.JACI 2009;123:417-23 Levels of peanut exposure by different routes between groups Outcome Eczematous children with egg allergy but not sensitize to peanut (n=160) , healthy controls (n=150) Compare Peanut exposure during first year of life during pregnancy, lactation and household peanut consumption Intervention (questionnaire before SPT) Eczematous children with peanut allergy aged under 48 months (n= 133) Patient
  45. 45. <ul><li>Diagnosis of PA : SPT wheal > 8 mm, a specific IgE > 15 kUA/L or positive DBPCFC </li></ul>** ** * 0 , 1.1, 2.4 g 0 , 0.6 , 0.9 g ** P<0.001 ** P<0.001 1.9 , 6.9 ,18.8 g * P=0.009 *** *** P=0.002 ฿ ฿ ฿ =NS
  46. 46. Fox et al.JACI 2009;123:417-23
  47. 47. Fox et al.JACI 2009;123:417-23
  48. 48. Comments for this paper <ul><li>Is it truely possible to discriminate between household </li></ul><ul><li>and peanut consumption?? </li></ul><ul><li>Maternal consumption was included in household </li></ul><ul><li>consumptions </li></ul>
  49. 49. Subgroup analysis of high-risk controls <ul><li>Median environmental exposure was very low </li></ul><ul><li>But 11% more than 20 g/week </li></ul><ul><li>1.9% more than 50 g/week </li></ul><ul><li>Why do they develop peanut allergy? </li></ul><ul><li>Milder eczema </li></ul>
  50. 50. <ul><li>These data allow early consumption of peanut protein, but they do not provide sufficient evidence to suggest that it has a protective effect or that environmental exposure to peanut puts children at risk </li></ul>A. Wesley Burks . JACI 200 9 ; 123 (2) : 424 – 5
  51. 51. <ul><li>4 male , 9-13 years , did DBPCFC to confirmed diagnosis and pretreatment threshold doses </li></ul><ul><li>OIT was done by peanut flour mixed with yogurt dose 5-800 mg , conventional protocol </li></ul><ul><li>Increasing dose every 2 weeks </li></ul><ul><li>Maintainace dose 800 mg protein after post OIT challenge </li></ul><ul><li>Follow-up studies are required to examine the duration and frequency of maintenance therapy required to induce long-term tolerance </li></ul>Clark et al.Allergy 2009.Feb 17; ePub ahead of Print
  52. 52. Clark et al.Allergy 2009.Feb 17; ePub ahead of Print
  53. 53. 6 weeks after final dose Clark et al.Allergy 2009.Feb 17; ePub ahead of Print
  54. 54. Take Home Message <ul><li>Indicence of peanut allergy seems to be rising without explanation </li></ul><ul><li>Peanut and other legumes : clinical cross-reactions are unlikely to occur </li></ul><ul><li>Peanut and treenut : no DBPC study but still should recommend to avoid </li></ul>
  55. 55. Take Home Message <ul><li>Factors associated developing peanut allergy </li></ul><ul><li>- Soybean consumption in early infant </li></ul><ul><li>- Applying peanut oil in eczematic skin </li></ul><ul><li>- Delayed consumption in infancy ?? </li></ul><ul><li>- Enviromnental exposure via household </li></ul><ul><li>consumption?? </li></ul><ul><li>SOTI seems to be promising treatment </li></ul>
  56. 56. Thank You for Your Attention

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